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Epilepsy is a severe neurological condition affecting 50–65 million individuals worldwide that can lead to brain damage. Nevertheless, the etiology of epilepsy remains poorly understood. Meta-analyses of genome-wide association studies involving 15,212 epilepsy cases and 29,677 controls of the ILAE Consortium cohort were used to conduct transcriptome-wide association studies (TWAS) and protein-wide association studies (PWAS). Furthermore, a protein-protein interaction (PPI) network was generated using the STRING database, and significant epilepsy-susceptible genes were verified using chip data. Chemical-related gene set enrichment analysis (CGSEA) was performed to determine novel drug targets for epilepsy. TWAS analysis identified 21,170 genes, of which 58 were significant (TWASfdr < 0.05) in ten brain regions, and 16 differentially expressed genes were verified based on mRNA expression profiles. The PWAS identified 2249 genes, of which 2 were significant (PWASfdr < 0.05). Through chemical-gene set enrichment analysis, 287 environmental chemicals associated with epilepsy were identified. We identified five significant genes (WIPF1, IQSEC1, JAM2, ICAM3, and ZNF143) that had causal relationships with epilepsy. CGSEA identified 159 chemicals that were significantly correlated with epilepsy (Pcgsea < 0.05), such as pentobarbital, ketone bodies, and polychlorinated biphenyl. In summary, we performed TWAS, PWAS (for genetic factors), and CGSEA (for environmental factors) analyses and identified several epilepsy-associated genes and chemicals. The results of this study will contribute to our understanding of genetic and environmental factors for epilepsy and may predict novel drug targets.

Pulmonary embolism (PE) is a leading cause of death in stroke patients and a severe health burden worldwide. There is a pressing need to understand the mechanisms by which it occurs and to identify at-risk patients efficiently and accurately.First, based on data from GWAS in European populations, we performed a linkage disequilibrium score regression (LDSC) analysis of plasma proteins and PE in 3,283 individuals and additionally analyzed the genetic association between PE and fracture. Then, we performed a TWAS on PE GWAS data using skeletal muscle and blood for gene expression references. Finally, we validated the genetic correlation between PE and human plasma proteins by co-matching the genes encoding the identified proteins and those identified using TWAS with the differentially expressed genes obtained from mRNA expression profiling of PE.We identified five plasma proteins associated with PE, including hydroxycarboxylic acid receptor 2, defensin 118, and bone morphogenetic protein (BMP) 7, as well as a relationship between PE and fracture. Comparison of genes encoding these proteins with genes obtained from TWAS and then with differentially expressed genes obtained from PE mRNA expression profiling revealed that PE was highly correlated with the BMP family of genes.

The main treatments for Parkinson's disease (PD) currently include surgery, rehabilitation, and most commonly, drug therapy. However, the drugs that are currently used to treat PD provide only symptomatic relief and delayed disease progression but have no curative effect and cause many adverse reactions. When considering pathogenic factors and metabolic regulation, PD and type 2 diabetes have a high rate of comorbidity; this provides a theoretical basis for the treatment of PD with first-line antidiabetic drugs. Among these agents, metformin reduces neuronal damage in the brains of PD patients via neuroprotection and the inhibition of oxidative stress and inflammatory responses, thus providing a novel strategy for the clinical treatment of PD. Here, we present the current state of knowledge about the use of metformin to treat PD and discuss its clinical prospects.

The Food Frequency Questionnaire (FFQ) is often used to assess dietary intake in large-scale epidemiological studies. This study aimed to evaluate the reproducibility and validity of the FFQ newly developed for children aged 6 to 12 in western China. A total of 133 children were included in the analysis, and all the children and their caregivers completed the FFQs twice with a three-month interval period, and three 24 h recalls were carried out one month after the first FFQ. We assessed the relative validity and reproducibility using various methods, such as the Spearman correlation coefficient, intra-class correlation coefficient, weighed Kappa, quartile agreement, and Bland–Altman analysis. The Spearman correlation coefficients for food ranged from 0.30 to 0.84, and for nutrients from 0.46 to 0.82 regarding reproducibility. The food intra-class correlation coefficients ranged from 0.20 to 0.85, while nutrients’ ranged from 0.37 to 0.75. In terms of relative validity, the average Spearman correlation coefficients for food were 0.20, and 0.30 for energy and nutrients. The energy-adjusted and de-attenuation coefficients were calculated. Moreover, the average percentage of participants misclassified into the extreme quartile for food and nutrients was 8.0% and 7.0%, respectively. Weighted Kappa values indicated acceptable agreement between the FFQs and 24 h recalls. Furthermore, the percentage of results in the limits of agreement (LOA) were all above 93.0%. In conclusion, The FFQ showed good reproducibility and acceptable relative validity for assessing the dietary intake of children aged 6–12 in western China.

Osteoarthritis (OA), the most common type of arthritis, is an age-associated disease, characterized by the progressive degradation of articular cartilage, synovial inflammation, and degeneration of subchondral bone. Chondrocyte proliferation is regulated by the Indian hedgehog (IHH in humans, Ihh in animals) signaling molecule, which regulates hypertrophy and endochondral ossification in the development of the skeletal system. microRNAs (miRNAs, miRs) are a family of about 22-nucleotide endogenous non-coding RNAs, which negatively regulate gene expression. In this study, the expression level of IHH was upregulated in the damaged articular cartilage tissues among OA patients and OA cell cultures, while that of miR-199a-5p was the opposite. Further investigations demonstrated that miR-199a-5p could directly regulate IHH expression and reduce chondrocyte hypertrophy and matrix degradation via the IHH signal pathway in the primary human chondrocytes. The intra-articular injection of synthetic miR-199a-5p agomir attenuated OA symptoms in rats, including the alleviation of articular cartilage destruction, subchondral bone degradation, and synovial inflammation. The miR-199a-5p agomir could also inhibit the Ihh signaling pathway in vivo. This study might help in understanding the role of miR-199a-5p in the pathophysiology and molecular mechanisms of OA and indicate a potential novel therapeutic strategy for OA patients.

Background The incidence of pulmonary embolism complications in the literature ranges from 10 to 50%, with a 0.5–10% risk of fatal pulmonary embolism. However, the biological cause of pulmonary embolism is unknown. Methods This study used data from the Genome-Wide Association Study (GWAS) of Pulmonary Embolism and Human Blood Metabolites from the UK Biobank, and the data from subjects of European ancestry were analyzed. We explored the relationship between pulmonary embolism and blood metabolites in three ways. We first analyzed the genetic correlation between pulmonary embolism and human blood metabolites using the linkage disequilibrium score regression (LDSC) and then analyzed the causal relationship between pulmonary embolism and meaningful blood metabolites obtained from the LDSC, a procedure for which we used Mendelian randomization analysis. Finally, we obtained transcriptome sequencing data for patients with a pulmonary embolism from the GEO database, analyzed differentially expressed genes (DEGs) in patients with pulmonary embolism versus healthy populations, and compared the DEGs with the resulting blood metabolite genes to further validate the relationship between pulmonary embolism and blood metabolites. Result We found six human blood metabolites genetically associated with pulmonary embolism, stearic acid glycerol phosphate ethanolamine (correlation coefficient = 0.2582, P = 0.0493), hydroxytryptophan (correlation coefficient = 0.2894, P = 0.0435), and N1-methyladenosine (correlation coefficient = 0.0439, P = 0.3728), and a significant causal relationship was discovered between hydroxytryptophan and pulmonary embolism. After screening microarray data from the GEO database, we performed differential gene analysis on the GSE19151 dataset and screened a total of 22,216 genes with P values less than 0.05, including 17,361 upregulated genes and 4854 downregulated genes. By comparing the resulting differentially expressed genes with six genes encoding blood metabolites, LIPC and NAT2 were found to be differentially expressed in association with pulmonary embolism.

Fluorinated organic chemicals have a wide variety of industrial and consumer applications. For long time perfluorooctane sulfonate and perfluorooctanoic acid have been used as precursors for manufacture of such chemicals. However, these C8 chain compounds have been demonstrated to be toxic, persistent, and bioaccumulative, thus inducing their phase-out. Currently, C6 telomer based fluorocarbon surfactants are considered better alternatives to C8 products because of their low bioaccumulability. But, their high persistency suggests that in the near future their concentrations will increase in the environment and in industrial waste. Being a solid state non-thermal technology, mechanochemical treatment is a good candidate for the destruction of emerging C6 fluorotelomers in solid waste. In the present study, 6:2 fluorotelomer sulfonate is effectively destroyed (~100%) in rapid manner (2 “flake-off” process through radical mechanism.

The destruction of persistent organic pollutants (POPs) is a large challenge in particular in developing and emerging economies. To date, a detailed assessment of non-combustion technologies with respect to formation of dioxins is lacking. In this study, an assessment of mechanochemical (MC) destruction technology for polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in contaminated soil remediation was conducted. Actual applied conditions of pilot-scale MC POPs destruction process indicates that the temperature increase inside the ball mills has the potential to form high levels of toxic polybrominated and polychlorinated dibenzo-p-dioxins and dibenzofurans (PXDD/Fs) when dioxin precursors are present. Therefore, the MC technology was modified for treatment of the PCB and PBDE containing soil including an efficient cooling system which could prevent the formation of PXDD/F during the destruction of PCBs and PBDEs. This is likely relevant for all contaminated soils containing relevant dioxin precursor and need to be considered for treatment of soils with MC and probably other non-combustion technologies. Graphical abstract ᅟ.

Perfluorinated chemicals (PFCs) are attracting increasing concern due to their chemical stability and toxicity, which make them classifiable as persistent organic pollutants. However, such compounds are employed for the manufacture of many industrial and consumer products, hence their substitution is not possible in the near future. Suitable technologies for PFCs environmentally sound management are necessary. High energy ball milling with KOH has been proved to obtain PFCs safe destruction, but with excessive reagent. In the present study, a Waste-to-Materials solution is proposed: PFCs are co-milled with stoichiometric amounts of La2O3 and thus are fully converted into LaOF, a noteworthy luminescent material with many potential industrial applications. Reaction mechanism is also investigated: Ball milling process activates La2O3; this latter provokes oxidation to CO2 and carbonization of PFCs; fluorides are incorporated into the La2O3’s lattice to form the oxyfluoride. Interestingly, kinetic analysis suggests that the mechanical activation of La2O3 might follow a zeroth-order reaction rate.

IntroductionTake-away milk tea (TAMT) is popular among young generation, and the numbers of retails of TAMT have increased dramatically in recent years in many cities in China. Non-dairy cream is one of the major ingredients of TAMT. Concerns have been raised whether trans-fat originated from non-dairy cream may have an influence on cardio-metabolic traits. We evaluated the associations between daily intake of TAMT with plasma lipid profiles among young Chinese adults, who are the major customers of TAMT retailers.Materials and MethodsThe study population was from the phase 1 sample (104 adults) of the Carbohydrate Alternatives and Metabolic Phenotypes study. Those lacking blood samples or with a body mass index less than 18.5 kg/m2 were excluded, therefore, a total of 88 subjects with an average age of 22.8 years were included in the analysis. A food frequency questionnaire with 27 items was used to collect the dietary intake. Generalized linear regression was used to evaluate the associations between TAMT intake and cholesterol levels.ResultsThe estimated mean (± SE) of TAMT intake was 14.4 ± 3.4 ml/day, with apparent differences between males (8.8 ± 2.7 ml/day) and females (17.7 ± 5.1 ml/day). The mean of total cholesterol of the participants was 4.1 ± 0.1 mmol/L. After adjusted for age, sex, education attainment, smoking status, alcohol drink habit, and physical activity level, daily TAMT intake was positively associated with total cholesterol (beta ± SE = 0.0053 ± 0.0020, P = 0.011). The association was not substantially changed with further adjustment of body fat percentage (beta ± SE = 0.0053 ± 0.0020, P = 0.010). Similar associations were observed for high/low density lipoprotein cholesterols. When analysis was performed by sex, the association was only observed among females (beta ± SE = 0.0049 ± 0.0022, P = 0.031), but not in males (beta ± SE = 0.0022 ± 0.0060, P = 0.703).ConclusionIn young adult Chinese, we observed an association between TAMT intake with plasma cholesterol level, independent of body adiposity.

A novel mechano-synthesis method has been elaborated in this work for the design of efficient cobalt-based Fischer–Tropsch catalysts. The process aims to reduce the total number of steps involved in the synthesis of solid catalysts and thus to avoid relevant toxic solutions generated during the catalyst preparation. The mechano-synthesis of the Co/Al2O3 catalyst was processed in a low-energy vibratory micro mill and high energy planetary ball mill. Porous spherical γ-aluminas (1860 µm and 71 µm mean particle diameter) were used in this work as host compounds. Co3O4 (3 µm mean particle diameter) has provided guest particles for mechano-synthesis. The catalysts were characterized by textural (surface area, porosity and particle size) and structural analyses (X-ray diffraction, TPR, SEM-EDX and microprobe). The microprobe images show deposition of Co3O4 on the surface of the alumina and indicated no Co3O4 diffusion inside the alumina pores. SEM-EDX mapping illustrated that cobalt coating tended to occur on surface of rounded shape of cracked alumina fragments. After milling, the crystallite size of Co3O4 decreased to 15 nm from 30 to 50 nm. The TPR profiles indicated very low concentrations of inactive cobalt aluminate mixed compounds which are usually produced during the catalyst preparation by impregnation. In Fischer–Tropsch synthesis, the catalysts prepared using mechano-synthesis methods showed catalytic performance comparable to the catalysts prepared by impregnation.

Genetic risk score (GRS, also known as polygenic risk score) analysis is an increasingly popular method for exploring genetic architectures and relationships of complex diseases. However, complex diseases are usually measured by multiple correlated phenotypes. Analyzing each disease phenotype individually is likely to reduce statistical power due to multiple testing correction. In order to conquer the disadvantage, we proposed a principal component analysis (PCA)–based GRS analysis approach. Extensive simulation studies were conducted to compare the performance of PCA-based GRS analysis and traditional GRS analysis approach. Simulation results observed significantly improved performance of PCA-based GRS analysis compared to traditional GRS analysis under various scenarios. For the sake of verification, we also applied both PCA-based GRS analysis and traditional GRS analysis to a real Caucasian genome-wide association study (GWAS) data of bone geometry. Real data analysis results further confirmed the improved performance of PCA-based GRS analysis. Given that GWAS have flourished in the past decades, our approach may help researchers to explore the genetic architectures and relationships of complex diseases or traits.

Mechanochemical activation of metal oxides is studied by a novel methodology based on solid state reaction with a stable radical specie. Such approach corroborates that vacancy formation by high energy ball milling, also in nonreducible oxides, is responsible for electron release on particles’ surfaces. This finding suggests a new defect engineering strategy to improve effectiveness of metal oxides as co-milling reagent for halogenated organic pollutant destruction. Results prove that high valent metal doping of a commonly employed co-milling reagent such as CaO determines 2.5 times faster pollutant degradation rate. This enhancement is due to electron-rich defects generated by the dopant; electrons are transferred to the organic pollutant thus causing its mineralization. The proposed strategy can be easily applied to other reagents.

This preliminary study examined the role of microwave radiation on precipitation and aging of iron oxyhydroxides at 60 °C. It was observed that due to rapid heating under microwave, transformation of two line ferrihydrite to α-Fe2O3 takes place within 4–10 h. This is in contrast to the usual aging temperature of > 100 °C adopted in most conventional studies, and several days of aging. Besides rapid transformation, microwave helps forming nanoparticles, with crystallite size of ~ 60 nm as determined from X-ray diffractograms, and < 100 nm particles as observed under TEM. Rapid transformation also promotes formation of α-Fe2O3 without the formation of intermediate γ-Fe2O3. This study brought out the advantages of low temperature microwave assisted precipitation/aging as a low energy process to transform iron oxyhydroxides, with likely applications in slurry rheology, synthesis of nanoparticles, and adsorption.

In this work, alumina-supported cobalt (Co/Al2O3) catalysts were prepared using new solvent-free mechanochemical synthesis methods: low-energy vibratory ball milling (Fritsch, Pulverisette 0) and high-energy planetary ball milling (Retsch, PM 100). γ-Al2O3 supports and Co/Al2O3 catalysts after mechanochemical treatments were characterized using a combination of techniques. The study of solid particles revealed the abrasion and fragmentation phenomena of porous γ-Al2O3 particles and pore filling under milling. Functional cobalt particles introduced by the mechanochemical synthesis were observed to be preferentially localized on the outer surface of the alumina supports. High Fischer–Tropsch reaction rates were obtained with the catalysts prepared by optimized mechanochemical synthesis conditions. The enhanced catalytic performance can be attributed to the relatively high dispersion of cobalt and the absence of inert cobalt aluminates which are usually present in the catalysts synthesized by the conventional impregnation.

A novel method for preparation of iron oxyhydroxide materials, involving aqueous precipitation followed by microwave assisted aging is investigated. The produced materials are characterized by XRD, SEM, EDX and TEM spectroscopy and BET analysis. The materials show physical characteristics dependent on preparation procedure. The adsorptive properties of the materials for arsenic are studied by batch adsorption techniques. It is found that the rate of arsenic upload depends strongly on the degree of crystallinity of the materials. The adsorption capacity is approximately 55 mg/g. The physical characterization of the arsenic loaded adsorbents show that the adsorption process modifies the morphology of the materials. Over 4% of arsenic atoms are incorporated into the particle matrix.